Valve Formation

One goal of the lab is to identify the genes needed for cushion and valve formation in mouse. Congenital aortic valve defects occurs in 2%-3% of the population. Pulmonary valvular disease also constitutes 10% of all congenital heart disease in adults (Brickner et al., 2000). Most of these congenital defects do not produce disease until midlife, when they generate significant morbidity. Congenital valve disease thus provides an example of how aberrant embryonic processes can lead to disease in mid and late adulthood (Garg et al., 2005). Understanding the mechanisms governing valve development could thus lead to therapeutic strategies to prevent congenital heart defects as well as repair valves defects. In diseased heart valves, there is distinct loss of extra-cellular matrix (ECM) organization associated with changes in mechanical proprieties that ultimately leads to dysfunction (Schoen, 2005). However, the molecular events that result in aberrant ECM expression and distribution characteristic of valve disease are largely unknown. We have recently discovered that the zinc finger containing transcription factor Krox20/Egr-2, a critical regulator of hindbrain development, is required for aortic valve development and for ECM organization.

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